# Neuroplasticity of the Extended Amygdala CRF circuitry in alcohol dependence

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $399,375

## Abstract

Alcohol use disorder (AUD) is a major public health concern characterized by the loss of control over
alcohol drinking and the emergence of negative emotionality during abstinence from alcohol. The
transition to alcohol dependence is associated with the concomitant dysregulation of executive function
by the medial prefrontal cortex (mPFC) and the recruitment of corticotropin releasing factor (CRF) and
its CRF receptor 1 (CRF1) in the central nucleus of the amygdala (CeA), but much less is known about
the role of CRF/CRF1 signaling in cortical areas. Critically, the development of new tools to access
subpopulations of CRF1 neurons has facilitated our studies of function and connectivity of CRF/CRF1
systems. In the original grant, we use an innovative transgenic mouse models in which CRF1
expressing (CRF1+) neurons co-express green fluorescent protein (GFP) (CRF1:GFP mice) to
understand the cell type-specific effects of acute and chronic alcohol in local and downstream CeA
microcircuits. Preliminary data have revealed that the CRF1+ neurons are highly expressed in mPFC
layer 2/3 and undergo specific neuroadaptations following chronic alcohol compared to unlabeled
(CRF1-) neurons. Thus, in this renewal, we will continue to use CRF1:GFP and CRF1:Cre mice to
characterize the electrophysiological, neurochemical and morphological properties of both CRF1+ and
CRF1- neurons in the mPFC, and elucidate the role of mPFC CRF1+ circuitry in anxiety-like and
drinking behaviors. Through a systems biology approach, we will delineate the CRF1-dependent effects
of ethanol in mPFC, as well as amygdala-mPFC connectivity that may regulate ethanol dependence
and withdrawal and contribute to associated anxiety-related behaviors. In addition, we will use
fluorescence activated cell sorting (FACS) followed by whole transcriptome analysis to reveal molecular
signatures and neuroadaptations of this specific CRF1 cortical population, which may identify new
promising targets for treatment strategies for alcoholism.

## Key facts

- **NIH application ID:** 10543780
- **Project number:** 5R01AA021491-09
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** MARISA ROBERTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $399,375
- **Award type:** 5
- **Project period:** 2013-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543780

## Citation

> US National Institutes of Health, RePORTER application 10543780, Neuroplasticity of the Extended Amygdala CRF circuitry in alcohol dependence (5R01AA021491-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10543780. Licensed CC0.

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